This K24 Midcareer Investigator Award in Patient-Oriented Research is a competitive renewal that will provide five years of support to enhance a program of research and mentoring for the applicant in Neuroimaging in Depression Treatment Studies. Major depression in late life is an important health problem with a large and growing number of affected individuals. A progress report describes important mentoring and research activities to date. During the current K24 award period we have provided mentoring through involvement of mentees in ongoing NIH grants, through consultation to faculty members on neuroimaging techniques and through R25, K12 and K30 initiatives. Findings in ongoing studies include: 1) Late life depression (LLD) subjects have significantly greater white matter hyperintensities interrupting specific regional pathways involved in mood regulation; 2) In addition, using fMRI and PET, we have identified disruptions in emotional circuitry and 3) regional loss of 5-HT2A receptors. The applicant has completed career development activities described in the previous application in diffusion tensor imaging, resulting in a new NIMH initiative and a NARSAD Independent Investigator Award. The overall goals of the applicant's research remain the same: 1) To engage in teaching and training activities that will help produce the next generation of clinical researchers in the area of geriatric psychiatry neuroimaging research; 2) To obtain career development training that will enhance an ongoing program of research; and 3) To continue to conduct an ongoing program of research studies focused on neuroimaging in depression treatment studies. The proposal describes the applicant's current research program and the career development and mentoring activities planned for the 5-year renewal of the K24. Three NIH grants are ongoing: one will determine if severity of WMH and frontal executive dysfunction predict less antidepressant treatment response; another measures dysregulation of emotional circuitry in depression and a third investigates amyloid abnormalities in LLD. A NARSAD grant will determine if LLD subjects have decreased white matter connectivity in important pathways involved in emotional regulation. Career development activities are described for the PI to learn functional connectivity mapping and to apply these measures in ongoing research studies. Trainees will engage in these projects, take coursework in neuroimaging and clinical investigation and complete a research proposal over the 2-year training period. K24 support will provide the applicant with protected time to continue to carry out depression studies in late life depression and to increase the mentoring of beginning clinical investigators in neuroimaging studies in depression. [unreadable] [unreadable] [unreadable]